AIM To compare the effects of Shaoling Formula emulsion versus its decoction on epidermal barrier function in a psoriasis mouse model.METHODS The Shaoling Formula emulsion was prepared by emulsification,whereas the decoction was produced by aqueous extraction.A psoriasis-like mouse model was established by topical application of 5％imiquimod cream(50 mg).The mice were randomly assigned to normal control,model control,Shaoling Formula emulsion group(13.26 g/kg),Shaoling Formula decoction group(13.26 g/kg),blank emulsion group,and positive control group(calcipotriol betamethasone ointment group,2.5 g/kg).After treatment for six consecutive days,the mice had their severity of skin lesions assessed with psoriasis area and severity index(PASI)scoring.Upon the completion of the treatment,the mice had transepidermal water loss(TEWL)and stratum corneum hydration(SCH)determined by the GPSkin Barrier;their histopathological changes in skin lesions observed using HE staining;their levels of TNF-α,IL-6,IL-17A,IL-22,and IL-23 in lesions detected by ELISA;and their Aquaporin 3(AQP3)expression analyzed by Western blot.RESULTS Compared to the model group,both the Shaoling Formula emulsion and positive control group demonstrated significant reductions in PASI scores(P＜0.01)and increased SCH(P＜0.01);decreased serum levels of TNF-α,IL-6,IL-17A,IL-22 and IL-23(P＜0.05,P＜0.01);histopathological improvements including attenuated parakeratosis/hyperkeratosis,reduced acanthosis,diminished dermal inflammatory cell infiltration,and normalized vasodilation;and upregulated AQP3 expression(P＜0.05).The Shaoling Formula decoction group exhibited reduced PASI scores(P＜0.01);and increased SCH(P＜0.05);decreased levels of IL-6,IL-17A,IL-22 and IL-23 in skin lesions(P＜0.05,P＜0.01).Notably,the emulsion group exhibited higher AQP3 protein expression than the decoction group(P＜0.05).CONCLUSION Shaoling Formula emulsion outperforms its decoction in restoring epidermal barrier function in psoriatic mice.This superiority is mechanistically linked to enhanced AQP3 protein expression and improved SCH.

Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

OBJECTIVE: To identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance. METHODS: A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument. Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System (FDAS) and Tongue Diagnosis Analysis System version 2.0 (TDAS v2.0). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Ten machine learning models and one deep learning model (ResNet50V2 + Conv1D) were developed and evaluated. RESULTS: Anemic women showed lower a-values, higher L- and b-values across all age groups. Texture features analysis showed that women aged 30-39 with anemia had higher angular second moment (ASM)and lower entropy (ENT) values in facial images, while those aged 40-49 had lower contrast (CON), ENT, and MEAN values in tongue images but higher ASM. Anemic women exhibited age-related trends similar to healthy women, with decreasing L-values and increasing a-, b-, and ASM-values. LASSO identified 19 key features from 62. Among classifiers, the Artificial Neural Network (ANN) model achieved the best performance [area under the curve (AUC): 0.849, accuracy: 0.781]. The ResNet50V2 model achieved comparable results [AUC: 0.846, accuracy: 0.818]. CONCLUSION Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
Humans ; Female ; Tongue/diagnostic imaging* ; Adult ; Anemia/diagnosis* ; Middle Aged ; Face/diagnostic imaging* ; Young Adult ; Machine Learning

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.

Objective:To build an evaluation index system for Huimin Insurance and provide reference for promoting the steady and sustainable development of Huimin Insurance.Methods:The evaluation indicators were initially constructed through literature analysis method and further revised and improved.The entropy weight TOPSIS method was used to evaluate and analyze 84 Huimin Insurance products with complete evaluation indicator data in 21 provinces across the country.Results:The constructed evaluation index system for Huimin Insurance includes 4 first-level indicators,10 second-level indicators and 28 third-level indicators.The weights of the first-level indicators,from high to low,are the sustainability indicator of Huimin Insurance(0.335 0),the guarantee ability indicator(0.235 1),the fairness indicator of participation in insurance(0.229 9)and the guarantee level indicator(0.200 0).The evaluation results show that the top ranked products are mainly concentrated in Zhejiang and Guangdong.Conclusion:The evaluation results of the entropy weight TOPSIS method are suitable for the comprehensive evaluation of Huimin Insurance and are comprehensive and scientific.They can be used to evaluate the operation and development of Huimin Insurance products,laying a good foundation for further evaluation of the sustainability of Huimin Insurance.

Objective To understand the current status of work-related musculoskeletal disorders (WMSDs) among operating room doctors,thereby analyzing its effect on mental health. Methods A total of 1013 doctors in the operating rooms of 30 hospitals in 24 provinces from September to December 2022 were selected by cross-sectional survey method. The domestic musculoskeletal disease questionnaire was used to investigate the occurrence of WMSDs in operating room doctors,the symptom check list-90 (SCL-90) was used to evaluate the psychological status of operating room doctors,the relationship between WMSDs related items and SCL-90 scores was analyzed,the correla-tion between the rest time of each shift and SCL-90 factors was analyzed by Pearson method,and the influencing factors of mental health of operating room doctors were analyzed by multivariate Logistic regression.Results A total of 1100 questionnaires were distributed and 1013 valid questionnaires were recovered,with an effective rate of 92.10％. The incidence of WMSDs among operating room doctors in the past 1 year was 95.06％. The body parts with incidences of WMSDs from high to low were as follows:waist (36.92％),neck (35.54％),shoulder (33.56％),and upper back (32.77％). In the past 1 year,the SCL-90 scores and total scores of patients with musculoskeletal pain in various body parts,keeping the same back posture for a long time while work,bending the back at the same time of turning frequently while working,bowing the head for a long time while working,and bending the knee for a long time while working were significantly higher than those who were without the above conditions (P<0.05). Shorter rest time of each shift and longer periods of keeping the same back posture were the risk factors for the development of mental illness in operating room doctors. Conclusion The incidence of WMSDs in operating room doctors is high,which can influence the mental health of operating room doctors. Therefore,operating room doctors should avoid keeping the same back posture for a long time,bending the back at the same time of turning frequently,bowing the head for a long time,and bending the knee for a long time while working,and increase the rest time of each shift,in order to improve the mental condition of the operating room doctors.

AIM To compare the effects of Shaoling Formula emulsion versus its decoction on epidermal barrier function in a psoriasis mouse model.METHODS The Shaoling Formula emulsion was prepared by emulsification,whereas the decoction was produced by aqueous extraction.A psoriasis-like mouse model was established by topical application of 5％imiquimod cream(50 mg).The mice were randomly assigned to normal control,model control,Shaoling Formula emulsion group(13.26 g/kg),Shaoling Formula decoction group(13.26 g/kg),blank emulsion group,and positive control group(calcipotriol betamethasone ointment group,2.5 g/kg).After treatment for six consecutive days,the mice had their severity of skin lesions assessed with psoriasis area and severity index(PASI)scoring.Upon the completion of the treatment,the mice had transepidermal water loss(TEWL)and stratum corneum hydration(SCH)determined by the GPSkin Barrier;their histopathological changes in skin lesions observed using HE staining;their levels of TNF-α,IL-6,IL-17A,IL-22,and IL-23 in lesions detected by ELISA;and their Aquaporin 3(AQP3)expression analyzed by Western blot.RESULTS Compared to the model group,both the Shaoling Formula emulsion and positive control group demonstrated significant reductions in PASI scores(P＜0.01)and increased SCH(P＜0.01);decreased serum levels of TNF-α,IL-6,IL-17A,IL-22 and IL-23(P＜0.05,P＜0.01);histopathological improvements including attenuated parakeratosis/hyperkeratosis,reduced acanthosis,diminished dermal inflammatory cell infiltration,and normalized vasodilation;and upregulated AQP3 expression(P＜0.05).The Shaoling Formula decoction group exhibited reduced PASI scores(P＜0.01);and increased SCH(P＜0.05);decreased levels of IL-6,IL-17A,IL-22 and IL-23 in skin lesions(P＜0.05,P＜0.01).Notably,the emulsion group exhibited higher AQP3 protein expression than the decoction group(P＜0.05).CONCLUSION Shaoling Formula emulsion outperforms its decoction in restoring epidermal barrier function in psoriatic mice.This superiority is mechanistically linked to enhanced AQP3 protein expression and improved SCH.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.